Keeping the immune system in check helps the development of healthy gut bacteria.

Doctors and scientists have long known that infants have fragile immune systems. They lack a robust defense system against invading pathogens, developing one as they age. In general, this suggested that the infant immune system simply needs time to get stronger. But new research indicates that infants' immune response is actively being held down by immunosuppressive cells.

Some precursors to red blood cells are marked by the protein CD71. Doctors at the Children's Hospital in Cincinnati found that, in human umbilical cord blood and newborn mice, these cells make an enzyme called arginase-2 that actively inhibits the immune response. When they transferred immune cells from newborns into adult mice, they found that the cells themselves were fully functional and capable of ramping up an immune response in the adult environment. This shows that the key is how the immune cells are regulated, not whether the infant immune cells themselves are immature.

Why would infants be intentionally susceptible to infection? The answer comes from one of the hottest new fields in medical research—the microbiome.

The microbiome is science shorthand for all of the benign and beneficial microbes that live in our bodies, helping us digest food and keeping populations of pathogens in check so we don't get sick. In recent years, thanks to high-throughput DNA sequencing, scientists have learned just how vast and varied the microbes who call us home can be.

The several pounds of bacteria that you carry around every day play a complex role in your health, and ongoing research continues to explore the ways that the make-up of our microbiome might effect our susceptibility to everything from diabetes to cancer.

But babies are born without a microbiome because they've spent the past nine months in the sterile womb and their digestive system is a blank slate. The first order of business in life, literally, is to start collecting one's bacterial community—babies swallow some of the microbes present along the vaginal canal, and that becomes the beginning of their microbiome. This isn't just an accident; research has shown that pregnant women's bodies actually change so that they host different types of bacteria in their vaginas. This may be an evolutionary adaptation to give the infant the best biome possible. Babies born through cesarean section miss out on establishing some of those key species according to research.

For their part, the infants seen to be tamping down their immune response to allow the beneficial bacteria to establish themselves. Obviously, this also makes them more susceptible to infection from dangerous bacteria as well, so developing a healthy microbiome is a bit of a tradeoff. The authors of the Cincinnati hospital study call it "unfortunate by-product of the greater benefits of active suppression during this crucial developmental period, when tolerance to commensal microbes is more uniformly advantageous."

In their paper, published this week in Nature, the authors also write that they expect that this finding could spur further research on the mechanism for infant immunosuppression. The goal would be to work around it to protect infant's health in the short term while they are busy building a healthy mircobiome—which will hopefully keep them healthy in the long term.

26 Reader Comments

Seems like it wouldn't be all that difficult to take a vaginal swipe or two and manually transfer that fluid into the mouth of the C-section baby in order to help it get its microbiome started. Shouldn't obstetricians and midwives all be routinely doing that?

This subject was covered in "An Epidemic of Absence". Although not confirmed, vigeelebrun's observation is accurate:

"As of 2007, one-third of all infants were born via C-section in the U.S., a 50 percent increase over a decade earlier, and a mass diversion from the evolutionary norm. We don’t necessarily have to avoid C-sections to preclude altered microbial colonization. In this instance, you can have your cake and eat it, too. At the conference, rumors circulated (which I couldn’t ultimately confirm) that physicians in some parts of the world have become concerned enough by altered colonization patterns that they swab C-section newborns with their mothers’ vaginal secretions. That’s a nice workaround."

Velasquez-Manoff, Moises (2012-09-04). An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases (pp. 176-177). Scribner. Kindle Edition.

Seems like it wouldn't be all that difficult to take a vaginal swipe or two and manually transfer that fluid into the mouth of the C-section baby in order to help it get its microbiome started. Shouldn't obstetricians and midwives all be routinely doing that?

I can only imagine the looks the parents would give you if you'd forgotten to explain............

Fascinating research. The more we discover, the more the complexity of the interaction between genetics and the environment becomes apparent. With every new insight we realise that we actually know less than we thought we did!

That mouse pic looks amazing. I have usually seen them at that age in a group around the mother and not as an individual on a hand like that.

I wonder if it feels squishy and if the skin feels sticky or smooth?

Anyway to the topic, it is not just the gastrointestinal system the child is picking up, but the bacteria, spores, and viruses in the air. Every building and environment is different so the infants gets exposed to the different stuff in the air to learn to build an immunity to that stuff.

There is research on allergies whether children get exposed to the allergens at an earlier age would decrease the likely-hood of developing those allergies later.

It is like the end of the war of the worlds where..... depending on the version..... the aliens get killed by disease.

Seems like it wouldn't be all that difficult to take a vaginal swipe or two and manually transfer that fluid into the mouth of the C-section baby in order to help it get its microbiome started. Shouldn't obstetricians and midwives all be routinely doing that?

As fung81 said, it's not just the GI flora at issue. Recent studies showed that infants were born with flora in general that mimicked the vaginal tract (maybe also the fecal flora?) and as they grew their various floras evolved more into adult form (oral, skin, bowels, etc.) But generally yeah, seems like a great idea, and lots of exciting therapies to come, I expect.

...more recent studies (that I also can't find a link to) found that oral flora varies a lot depending on where in the mouth you check... that even the front and back of teeth have substantially different flora.

Seems like it wouldn't be all that difficult to take a vaginal swipe or two and manually transfer that fluid into the mouth of the C-section baby in order to help it get its microbiome started. Shouldn't obstetricians and midwives all be routinely doing that?

Many already do. They will swab the vagina with a Q-Tip and then put it inside the baby's mouth and stroke the cheek to transfer the bacteria.

I just tried unsuccessfully to find out whether the mass of the average persons bacterial load has changed significantly since we've known about microbiology. Changes in GI flora relating to animal domestication, agriculture, western diets etc. are well documented but does anyone know if changes in the population of our passengers has been looked at?

I just tried unsuccessfully to find out whether the mass of the average persons bacterial load has changed significantly since we've known about microbiology. Changes in GI flora relating to animal domestication, agriculture, western diets etc. are well documented but does anyone know if changes in the population of our passengers has been looked at?

My totally non-expert impression (simply from enthusiasm for the subject) is that the microbiome has barely been studied in detail, including the GI flora issues you mentioned. I'd be (pleasantly) surprised if your question has been answered. AFAIK the American Gut project and a couple similar efforts are the first (?) efforts to do a large-scale survey of the microbiome across different diets/lifestyles/genetics. Given all the amazing things being discovered about the importance of the microbiome, it's too bad we've neglected it so long.

Seems like it wouldn't be all that difficult to take a vaginal swipe or two and manually transfer that fluid into the mouth of the C-section baby in order to help it get its microbiome started. Shouldn't obstetricians and midwives all be routinely doing that?

I actually know of a family that did this with their first child. The swabbed both the vagina and anus for microbiota samples to colonize the C section baby. Sounds a little gross, but there have also been studies correlating mothers who defacte upon delivery pass on a healthier microbiome than mothers who dont.... so yeah

As of 2007, one-third of all infants were born via C-section in the U.S., a 50 percent increase over a decade earlier, and a mass diversion from the evolutionary norm. We don’t necessarily have to avoid C-sections to preclude altered microbial colonization. In this instance, you can have your cake and eat it, too.

Gross. Did they really have no other option besides a food-based idiom to make the point?

The mother produces antibodies in breast milk, and breast milk itself binds to pathogen to prevent infection, so the tradeoff of a weakened immune system isn’t without some other evolutionary support. And as a bonus, breastfeeding also helps populate the gut with the right kind of flora. As someone who has had three children, none of our babies ever got really sick while they were breastfeeding — not a single one got an ear infection.

It really is amazing how divorced from reality science and medicine became in the 20th century…partly because breasts are sex organs and that would be dirty. Apparently, they even failed basic anatomy.

As someone who has had three children, none of our babies ever got really sick while they were breastfeeding — not a single one got an ear infection.

It really is amazing how divorced from reality science and medicine became in the 20th century…partly because breasts are sex organs and that would be dirty. Apparently, they even failed basic anatomy.

Kids, give your babies breast milk, because science.

Plural of "anecdote" isn't "data" and all that -- I'm told that 'despite' breastfeeding, I was frequently sick, at least one cousin was the same, and my brother's 15-month-old is often ill as well. Our mothers all gave birth vaginally and were extremely careful to eat/drink as healthily as possible. (OTOH, once placed on prescription full nutrition-replacement due to persistent failure-to-thrive status, I wasn't sick at all.)

Repeated studies that followed kids from birth through childhood indicated that while there was a small difference in various things (development, allergies, etc.) early on, by kindergarten there was no reliable way to identify which kids had been breastfed and for how long. Disturbingly, there have been quite a few cases now where kids that weren't doing well on breastmilk landed in failure-to-thrive status because their parents were scared away from supplementing with anything else.

Helminthic Therapy. For those that don't know two species of intestinal parasites (worms) are "safe" (though not according to the FDA yet) for use in suppressing the immune system. These little guys attach to your gut wall and siphon about 0.1ml of blood a day and in return they inhibit your immune system to make their occupation easier. Research has been done by U of IA and Cambridge to try to isolate how these guys do it. But the results are stunning: remission of just about every type of immune-based disease.

Couple this with the research coming out about gut flora and just how important and complex they are, it may come to taking parasite eggs along with your multi-vitamin. Arthritis, allergies, Chron's disease, asthma are all cleared up with remission rates in studies of around 75%.

I think a huge amount of medical bills and ailments would be eliminated by having these buggers in you.

The two species selected for study do not reproduce in the body. Their eggs go out with stool and need to develop before being able to re-enter the body.

The mother produces antibodies in breast milk, and breast milk itself binds to pathogen to prevent infection, so the tradeoff of a weakened immune system isn’t without some other evolutionary support. And as a bonus, breastfeeding also helps populate the gut with the right kind of flora. As someone who has had three children, none of our babies ever got really sick while they were breastfeeding — not a single one got an ear infection.

It really is amazing how divorced from reality science and medicine became in the 20th century…partly because breasts are sex organs and that would be dirty. Apparently, they even failed basic anatomy.

Kids, give your babies breast milk, because science.

Same here. My oldest son never got sick while being breast fed. My youngest son got a cold once, that my oldest son brought home from pre-school while still being breast fed. My daughter (youngest of the three) also got a cold once while being breast fed

For both of the younger kids who got a cold while breast feeding, all the symptoms were much shorter in duration than myself, my wife or the older kids (none of us who were obvously breast feeding at the time). Typically about 36hrs or so.

My oldest was a c-section though due to a failed induction. 12 days late, and my wife developed severe fever and bronchitis about 6hrs after the induction started...which the midwife pulled the pitocin on as she had developed a 100F fever over the course of an hour...and her water broke litteraly 5 minutes after they stopped the pitocin, which meant now or never, so back on the pit. 103F overnight, cooling blankets, chest x-ray for fluid in my wife's lungs, the works. After 24hrs her utereus just gave up and pretty much stopped contracting at 8 1/2cm dialation. At least by that point her fever had finally broken, but she was just used up, so they had to do a c-section.

Second two kids were VBACs (I guess technically the third was a VBAAC since it was after, after a c-section :-P).

Interesting post there, Scop1us. Maybe we could produce sterile helminths so we don't end up infecting your family in a less-than-controlled way? Then we could buy off-the shelf equivalents of "live yoghurt". It has my vote.

Helminthic Therapy. For those that don't know two species of intestinal parasites (worms) are "safe" (though not according to the FDA yet) for use in suppressing the immune system. These little guys attach to your gut wall and siphon about 0.1ml of blood a day and in return they inhibit your immune system to make their occupation easier. Research has been done by U of IA and Cambridge to try to isolate how these guys do it. But the results are stunning: remission of just about every type of immune-based disease.

Couple this with the research coming out about gut flora and just how important and complex they are, it may come to taking parasite eggs along with your multi-vitamin. Arthritis, allergies, Chron's disease, asthma are all cleared up with remission rates in studies of around 75%.

I think a huge amount of medical bills and ailments would be eliminated by having these buggers in you.

The two species selected for study do not reproduce in the body. Their eggs go out with stool and need to develop before being able to re-enter the body.

Repeated studies that followed kids from birth through childhood indicated that while there was a small difference in various things (development, allergies, etc.) early on, by kindergarten there was no reliable way to identify which kids had been breastfed and for how long.

"

While some studies have slightly differing findings (such as adults with Crohn's are 60% less likely to have been breastfed), how children are in Kindergarten has little to do with the study we are discussing, on establishment of the infant microbiomes (though yes, it's been found that the very earliest microbiome development can have impact on the rest of one's life). Differences between exclusively breastfed infants and those receiving any formula are very distinctly measured and documented, and are greater, the younger the infant.

The addition of vaginal secretions to C-sect babies is a good idea.

Studies show that babies born in homes with healthy people develop healthier microbiomes than even vaginally born in hospitals -- full of unfavorable flora. The sooner mother's colostrum -- full of flora (and better flora the healthier mom is) and multitude other immune factors -- is introduced into baby, the healthier microbiome they are found to develop, with studies comparing minutes to hours. If newborns had completely active immune systems, they would likely be overwhelmed with reacting to the thousands of new microbes each day. Mother's milk is highly anti-inflammatory and brings in all of her experience with the microbial world; filling in with antibodies and many other immune-providing factors to compensate for baby's necessarily weaker immune system. Anecdotal examples are not useful, while multitude studies show that exclusively breastfed babies suffer about 1/3rd as many respiratory and Gi infections, and with shorter durations and less severity (in industrialized nations. The differences in developing world are far greater.) These are the illnesses that are most affected by flora. Introduction of even one bottle of formula provides free iron that feeds the more challenging microbes that are meant to be held back by exclusive breastmilk for many months, as baby's immune system gradually matures. Babies who have had much of anything besides human milk tend to be more like fully formula fed babies in studies of prevalence of illness.

Yes, antibiotics in meats we consume, high sugar, low fiber, other junky and simply drifting dietary practices, living in enclosed environments, and certainly all kinds of other factors have "evolved" our collective microbiomes to much less healthy ones that promote IBS, IBD, arthritis, ulcers, obesity, etc. Microbiome research is exciting, and in its infancy. I'm sure they will find valuable strains that are all but extinct in the modern world, but may be preserved for us in less-touched tribes. Ancient probiotics may be all the new rage one day.

Kate Prengaman / Kate is a science and environmental reporter living in Yakima, Washington. She writes about everything from emerging energy technology to persistent environmental problems and she really likes plants.